ATOVAQUONE
Clinical safety rating: safe
Animal studies have demonstrated safety
Atovaquone is a hydroxynaphthoquinone that selectively inhibits mitochondrial electron transport chain complex III (cytochrome bc1 complex) in parasites, thereby disrupting pyrimidine synthesis and energy metabolism.
| Metabolism | Hepatic metabolism via glucuronidation (UGT1A1, UGT1A9, UGT2B7) and to a lesser extent via CYP450 enzymes; undergoes enterohepatic recycling. |
| Excretion | Primarily fecal (>94%) as unchanged drug; renal excretion is minimal (<1%). |
| Half-life | Terminal elimination half-life is approximately 2-3 days (67 hours) in adults, prolonged in renal or hepatic impairment. |
| Protein binding | >99.9% bound, primarily to albumin. |
| Volume of Distribution | Approximately 0.6 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral tablet: 23% (fasted); increased approximately 1.5-fold with food (high-fat meal). |
| Onset of Action | Oral: Onset of clinical effect typically occurs within 24-48 hours of initiation. |
| Duration of Action | Duration correlates with half-life; therapeutic levels maintained with daily dosing. Clinical effect persists for several days after discontinuation. |
750 mg oral suspension twice daily for treatment of mild-to-moderate Pneumocystis jirovecii pneumonia; 1500 mg oral suspension once daily for prophylaxis.
| Dosage form | SUSPENSION |
| Renal impairment | No dosage adjustment required for renal impairment; atovaquone is highly protein-bound and not significantly renally excreted. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: caution due to limited data; Child-Pugh C: caution, monitor for toxicity (atovaquone is extensively metabolized in liver). |
| Pediatric use | For PJP prophylaxis: 30 mg/kg once daily (maximum 1500 mg) oral suspension; for PJP treatment: 40 mg/kg twice daily (maximum 1500 mg/dose) oral suspension. Use weight-based dosing with oral suspension (750 mg/5 mL). |
| Geriatric use | No specific dose adjustment based on age; use with caution in elderly due to potential for decreased hepatic function, renal function, and polypharmacy; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Metoclopramide and rifampin reduce plasma concentrations Should not be used for serious Pneumocystis pneumonia (PCP) in patients who cannot take it with food.
| Breastfeeding | Atovaquone is excreted into human breast milk in low concentrations; M/P ratio not determined. In 13 nursing women, milk concentrations were 0.8% of maternal serum levels. Due to potential for adverse effects in infants (e.g., anemia, rash), caution advised. Consider alternative therapy or pump and discard during treatment. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate human studies. In animal studies, atovaquone was not teratogenic in rats or rabbits at clinically relevant doses. However, increased fetal loss and maternal toxicity occurred at high doses. Due to lack of human data, risk cannot be ruled out. Use only if benefit outweighs risk, especially during organogenesis (first trimester). |
■ FDA Black Box Warning
None.
| Common Effects | Rash |
| Serious Effects |
History of hypersensitivity to atovaquone or any component of the formulation; concurrent use with rifampin or rifabutin (significant reduction in atovaquone plasma concentrations).
| Precautions | May cause potentially life-threatening hypersensitivity reactions (including angioedema, bronchospasm, anaphylaxis); hepatic toxicity (elevated liver enzymes, hepatitis); gastrointestinal adverse effects (nausea, vomiting, diarrhea); risk of breakthrough infection if doses are missed; use with caution in patients with hepatic or renal impairment. |
| Food/Dietary | High-fat meals significantly increase absorption (AUC increased up to 3-fold). Avoid taking with foods high in fiber or calcium (e.g., dairy products) simultaneously, as they may reduce absorption? administer with moderate-to-high fat meals. Consistent timing with food is recommended. |
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| Fetal Monitoring | Monitor maternal hepatic function (LFTs), renal function, and CBC periodically throughout therapy. In pregnancy, serial ultrasound for fetal growth assessment is recommended due to potential for maternal infection and drug effects. No specific fetal heart rate monitoring required. |
| Fertility Effects | No human data on fertility effects. In animal studies, atovaquone did not impair fertility in male or female rats at doses up to 1000 mg/kg/day. No evidence of altered spermatogenesis or oogenesis. |
| Clinical Pearls | Atovaquone is a second-line agent for Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment, often used when sulfa drugs are contraindicated. It requires administration with fatty food to enhance absorption (bioavailability increases 2-3 fold). Monitor for hepatotoxicity and rash. Not effective against toxoplasmosis due to poor CNS penetration. |
| Patient Advice | Take each dose with a fatty meal (e.g., eggs, cheese, milk) to improve absorption. · Complete the full course of therapy even if you feel better. · Report any signs of liver problems (yellowing skin/eyes, dark urine) or severe rash. · Store at room temperature; do not freeze the suspension. · Use effective contraception if applicable; atovaquone may reduce hormonal contraceptive efficacy. |